Associations between alcohol and cigarette use and type 1 and 2 myocardial infarction among people with HIV.

OBJECTIVES: People with HIV have a higher risk of myocardial infarction (MI) than the general population, with a greater proportion of type 2 MI (T2MI) due to oxygen demand-supply mismatch compared with type 1 (T1MI) resulting from atherothrombotic plaque disruption. People living with HIV report a greater prevalence of cigarette and alcohol use than do the general population. Alcohol use and smoking as risk factors for MI by type are not well studied among people living with HIV. We examined longitudinal associations between smoking and alcohol use patterns and MI by type among people living with HIV. DESIGN AND METHODS: Using longitudinal data from the Centers for AIDS Research Network of Integrated Clinical Systems cohort, we conducted time-updated Cox proportional hazards models to determine the impact of smoking and alcohol consumption on adjudicated T1MI and T2MI. RESULTS: Among 13 506 people living with HIV, with a median 4 years of follow-up, we observed 177 T1MI and 141 T2MI. Current smoking was associated with a 60% increase in risk of both T1MI and T2MI. In addition, every cigarette smoked per day was associated with a 4% increase in risk of T1MI, with a suggestive, but not significant, 2% increase for T2MI. Cigarette use had a greater impact on T1MI for men than for women and on T2MI for women than for men. Increasing alcohol use was associated with a lower risk of T1MI but not T2MI. Frequency of heavy episodic alcohol use was not associated with MI. CONCLUSIONS: Our findings reinforce the prioritization of smoking reduction, even without cessation, and cessation among people living with HIV for MI prevention and highlight the different impacts on MI type by gender.

People with HIV have a higher risk of COVID-19 diagnosis but similar outcomes to the general population.

BACKGROUND: We investigated the effect of HIV on COVID-19 outcomes with attention to selection bias due to differential testing and comorbidity burden. METHODS: This was a retrospective cohort analysis using four hierarchical outcomes: positive SARS-CoV-2 test, COVID-19 hospitalization, intensive care unit (ICU) admission and hospital mortality. The effect of HIV status was assessed using traditional covariate-adjusted, inverse probability-weighted (IPW) analysis based on covariate distributions for testing bias (testing IPWs), HIV infection status (HIV-IPWs) and combined models. Among people living with HIV (PWH), we evaluated whether CD4 count and HIV plasma viral load (pVL) discriminated between those who did and those who did not develop study outcomes using receiver operating characteristic analysis. RESULTS: Between March and November 2020, 63 319 people were receiving primary care services at the University of California San Diego (UCSD), of whom 4017 were PWH. The PWH had 2.1 times the odds of a positive SARS-CoV-2 test compared with those without HIV after weighting for potential testing bias, comorbidity burden and HIV-IPW [95% confidence interval (CI): 1.6-2.8]. Relative to people without HIV, PWH did not have an increased rate of COVID-19 hospitalization after controlling for comorbidities and testing bias [adjusted incidence rate ratio (aIRR) = 0.5, 95% CI: 0.1-1.4]. PWH did not have a different rate of ICU admission (aIRR = 1.08, 95% CI: 0.31-3.80) or of in-hospital death (aIRR = 0.92, 95% CI: 0.08-10.94) in any examined model. Neither CD4 count nor pVL predicted any of the hierarchical outcomes among PWH. CONCLUSIONS: People living with HIV have a higher risk of COVID-19 diagnosis than those without HIV but the outcomes are similar in both groups.

Tobacco smoking and binge alcohol use are associated with incident venous thromboembolism in an HIV cohort.

BACKGROUND: People with HIV (PWH) are at increased risk of cardiovascular comorbidities and substance use is a potential predisposing factor. We evaluated associations of tobacco smoking and alcohol use with venous thromboembolism (VTE) in PWH. METHODS: We assessed incident, centrally adjudicated VTE among 12 957 PWH within the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort between January 2009 and December 2018. Using separate Cox proportional hazards models, we evaluated associations of time-updated alcohol and cigarette use with VTE, adjusting for demographic and clinical characteristics. Smoking was evaluated as pack-years and never, former, or current use with current cigarettes per day. Alcohol use was parameterized using categorical and continuous alcohol use score, frequency of use, and binge frequency. RESULTS: During a median of 3.6 years of follow-up, 213 PWH developed a VTE. One-third of PWH reported binge drinking and 40% reported currently smoking. In adjusted analyses, risk of VTE was increased among both current (HR: 1.44, 95% CI: 1.02-2.03) and former (HR: 1.44, 95% CI: 0.99-2.07) smokers compared to PWH who never smoked. Additionally, total pack-years among ever-smokers (HR: 1.10 per 5 pack-years; 95% CI: 1.03-1.18) was associated with incident VTE in a dose-dependent manner. Frequency of binge drinking was associated with incident VTE (HR: 1.30 per 7 days/month, 95% CI: 1.11-1.52); however, alcohol use frequency was not. Severity of alcohol use was not significantly associated with VTE. CONCLUSIONS: Current smoking and pack-year smoking history were dose-dependently associated with incident VTE among PWH in CNICS. Binge drinking was also associated with VTE. Interventions for smoking and binge drinking may decrease VTE risk among PWH.

Effective Human Immunodeficiency Virus Molecular Surveillance Requires Identification of Incident Cases of Infection.

BACKGROUND: Ending the human immunodeficiency virus (HIV) epidemic requires knowledge of key drivers of spread of HIV infection. METHODS: Between 1996 and 2018, 1119 newly and previously diagnosed, therapy-naive persons with HIV (PWH) from San Diego were followed. A genetic distance-based network was inferred using pol sequences, and genetic clusters grew over time through linkage of sequences from newly observed infections. Cox proportional hazards models were used to identify factors associated with the rate of growth. These results were used to predict the impact of a hypothetical intervention targeting PWH with incident infection. Comparison was made to the Centers for Disease Control and Prevention (CDC) Ending the HIV Epidemic (EHE) molecular surveillance strategy, which prioritizes clusters recently linked to all new HIV diagnoses and does not incorporate data on incident infections. RESULTS: Overall, 219 genetic linkages to incident infections were identified over a median follow-up of 8.8 years. Incident cluster growth was strongly associated with proportion of PWH in the cluster who themselves had incident infection (hazard ratio, 44.09 [95% confidence interval, 17.09-113.78]). The CDC EHE molecular surveillance strategy identified 11 linkages to incident infections a genetic distance threshold of 0.5%, and 24 linkages at 1.5%. CONCLUSIONS: Over the past 2 decades, incident infections drove incident HIV cluster growth in San Diego. The current CDC EHE molecular detection and response strategy would not have identified most transmission events arising from those with incident infection in San Diego. Molecular surveillance that includes detection of incident cases will provide a more effective strategy for EHE.

How Do Treatment Priorities Differ Between Patients in HIV Care and Their Providers? A Mixed-Methods Study.

Evidence suggests priorities differ between patients in HIV care and their providers regarding topics most important to address in care. At five U.S. sites, we asked patients and providers to prioritize 25 potential topic areas to address during routine visits, and invited patients to discuss selection rationale. Patients (n = 206) and providers (n = 17) showed high discordance in rank order priorities (X2 (24, 223) = 71.12; p < 0.0001). Patients ranked social domains such as HIV stigma highly; a higher proportion of providers prioritized substance use domains. HIV stigma was a higher priority for patients in care fewer than 6 years (Fisher's exact p = 0.0062), nonwhite patients (Fisher's exact p = 0.0114), and younger patients (Fisher's exact p = 0.0281). Patients' priorities differed between men and women (X2 (24, 188) = 52.89; p < 0.0001), white race vs. other races (X2 (24, 206) = 48.32; p = 0.0023), and Latinos vs. non-Latinos (X2 (24, 206) = 48.65; p = 0.0021). Interviews (n = 79) revealed perceived impact of social context on health and health behaviors.

One Size Fits (n)One: The Influence of Sex, Age, and Sexual Human Immunodeficiency Virus (HIV) Acquisition Risk on Racial/Ethnic Disparities in the HIV Care Continuum in the United States.

BACKGROUND: The United States National HIV/AIDS Strategy established goals to reduce disparities in retention in human immunodeficiency virus (HIV) care, antiretroviral therapy (ART) use, and viral suppression. The impact of sex, age, and sexual HIV acquisition risk (ie, heterosexual vs same-sex contact) on the magnitude of HIV-related racial/ethnic disparities is not well understood. METHODS: We estimated age-stratified racial/ethnic differences in the 5-year restricted mean percentage of person-time spent in care, on ART, and virally suppressed among 19 521 women (21.4%), men who have sex with men (MSM; 59.0%), and men who have sex with women (MSW; 19.6%) entering HIV care in the North American AIDS Cohort Collaboration on Research and Design between 2004 and 2014. RESULTS: Among women aged 18-29 years, whites spent 12.0% (95% confidence interval [CI], 1.1%-20.2%), 9.2% (95% CI, .4%-20.4%), and 13.5% (95% CI, 2.7%-22.5%) less person-time in care, on ART, and virally suppressed, respectively, than Hispanics. Black MSM aged ≥50 years spent 6.3% (95% CI, 1.3%-11.7%), 11.0% (95% CI, 4.6%-18.1%), and 9.7% (95% CI, 3.6%-16.8%) less person-time in these stages, respectively, than white MSM ≥50 years of age. Among MSM aged 40-49 years, blacks spent 9.8% (95% CI, 2.4%-16.5%) and 11.9% (95% CI, 3.8%-19.3%) less person-time on ART and virally suppressed, respectively, than whites. CONCLUSIONS: Racial/ethnic differences in HIV care persist in specific populations defined by sex, age, and sexual HIV acquisition risk. Clinical and public health interventions that jointly target these demographic factors are needed.

Mortality following myocardial infarction among HIV-infected persons: the Center for AIDS Research Network Of Integrated Clinical Systems (CNICS).

BACKGROUND: Persons with human immunodeficiency virus (HIV) have higher risks for myocardial infarction (MI) than the general population. This is driven in part by higher type 2 MI (T2MI, due to coronary supply-demand mismatch) rates among persons with HIV (PWH). In the general population, T2MI has higher mortality than type 1 MI (T1MI, spontaneous and generally due to plaque rupture and thrombosis). PWH have a greater burden of comorbidities and may therefore have an even greater excess risk for complication and death in the setting of T2MI. However, mortality patterns after T1MI and T2MI in HIV are unknown. METHODS: We analyzed mortality after MI among PWH enrolled in the multicenter, US-based Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort (N = 28,186). Incident MIs occurring between January 1, 1996, and December 31, 2014, were centrally adjudicated and classified as T1MI or T2MI. We first compared mortality following T1MI vs. T2MI among PWH. Cox survival analyses and Bayesian model averaging were then used to evaluate pre-MI covariates associated with mortality following T1MI and T2MI. RESULTS: Among the 596 out of 28,186 PWH who experienced MI (2.1%; 293 T1MI and 303 T2MI), mortality rates were significantly greater after T2MI (22.2/100 person-years; 1-, 3-, and 5-year mortality 39%, 52%, and 62%) than T1MI (8.2/100 person-years; 1-, 3-, and 5-year mortality 15%, 22%, and 30%). Significant mortality predictors after T1MI were higher HIV viral load, renal dysfunction, and older age. Significant predictors of mortality after T2MI were low body-mass index (BMI) and detectable HIV viral load. CONCLUSIONS: Mortality is high following MI for PWH and substantially greater after T2MI than T1MI. Predictors of death after MI differed by type of MI, reinforcing the different clinical scenarios associated with each MI type and the importance of considering MI types separately.

Cumulative Human Immunodeficiency Viremia, Antiretroviral Therapy, and Incident Myocardial Infarction.

BACKGROUND: People living with HIV are at risk of increased myocardial infarction (MI). Cumulative HIV viral load (VL) has been proposed as a better measure of HIV inflammation than other measures of VL, like baseline VL, but its associations with MI are not known. METHODS: The multisite Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort includes clinical data and centrally adjudicated MI with distinction between atheroembolic MI (type 1) and MI related to supply-demand mismatch (type 2). We examined CNICS participants who were not on antiretroviral therapy (ART) at enrollment. Cumulative VL (copy-days of virus) from 6 months after enrollment was estimated with a time-weighted sum using the trapezoidal rule. We modeled associations of cumulative and baseline VL with MI by type using marginal structural Cox models. We contrasted the 75% percentile of the VL distribution with the 25% percentile. RESULTS: Among 11,324 participants, 218 MIs occurred between 1996 and 2016. Higher cumulative VL was associated with risk of all MI (hazard ratio [HR] = 1.72; 95% confidence interval [CI] = 1.26, 2.36), type 1 MI (HR = 1.23; 95% CI = 0.78, 1.96), and type 2 MI (HR = 2.52; 95% CI = 1.74, 3.66). While off ART, cumulative VL had a stronger association with type 1 MI (HR = 2.13; 95% CI = 1.15, 3.94) than type 2 MI (HR = 1.25; 95% CI = 0.70, 2.25). Baseline VL was associated with all MI (HR = 1.60; 95% CI = 1.28, 2.01), type 1 MI (HR = 1.73; 95% CI = 1.26, 2.38), and type 2 MI (HR = 1.51; 95% CI = 1.10, 2.08). CONCLUSIONS: Higher cumulative and baseline VL is associated with all MI, with a particularly strong association between cumulative VL and type 2 MI.

Emulating a trial of joint dynamic strategies: An application to monitoring and treatment of HIV-positive individuals.

Decisions about when to start or switch a therapy often depend on the frequency with which individuals are monitored or tested. For example, the optimal time to switch antiretroviral therapy depends on the frequency with which HIV-positive individuals have HIV RNA measured. This paper describes an approach to use observational data for the comparison of joint monitoring and treatment strategies and applies the method to a clinically relevant question in HIV research: when can monitoring frequency be decreased and when should individuals switch from a first-line treatment regimen to a new regimen? We outline the target trial that would compare the dynamic strategies of interest and then describe how to emulate it using data from HIV-positive individuals included in the HIV-CAUSAL Collaboration and the Centers for AIDS Research Network of Integrated Clinical Systems. When, as in our example, few individuals follow the dynamic strategies of interest over long periods of follow-up, we describe how to leverage an additional assumption: no direct effect of monitoring on the outcome of interest. We compare our results with and without the "no direct effect" assumption. We found little differences on survival and AIDS-free survival between strategies where monitoring frequency was decreased at a CD4 threshold of 350 cells/µl compared with 500 cells/µl and where treatment was switched at an HIV-RNA threshold of 1000 copies/ml compared with 200 copies/ml. The "no direct effect" assumption resulted in efficiency improvements for the risk difference estimates ranging from an 7- to 53-fold increase in the effective sample size.

Do Symptoms of Depression Interact with Substance Use to Affect HIV Continuum of Care Outcomes?

Few studies examine how depression and substance use interact to affect HIV control. In 14,380 persons with HIV (PWH), we used logistic regression and generalized estimating equations to evaluate how symptoms of depression interact with alcohol, cocaine, opioid, and methamphetamine use to affect subsequent retention in care, maintaining an active prescription for ART, and consistent virologic suppression. Among PWH with no or mild depressive symptoms, heavy alcohol use had no association with virologic suppression (OR 1.00 [0.95-1.06]); among those with moderate or severe symptoms, it was associated with reduced viral suppression (OR 0.80 [0.74-0.87]). We found no interactions with heavy alcohol use on retention in care or maintaining ART prescription or with other substances for any outcome. These results highlight the importance of treating moderate or severe depression in PWH, especially with comorbid heavy alcohol use, and support multifaceted interventions targeting alcohol use and depression.

Development and content validation of the Multifactoral assessment of perceived social support (MAPSS), a brief, patient-reported measure of social support for use in HIV care.

Low perceived social support (SS) negatively impacts health outcomes. We developed a measure of perceived SS for use in HIV care. We sought and categorized legacy items, selecting strongest items within categories. We elicited SS concepts from patients in English/Spanish, coded transcripts to match item pool content, and developed new items for salient unrepresented content. In focus groups, patients prioritized highly-matched items. We conducted cognitive interviews on high-priority items, and validity testing on final items against two legacy measures. From interviews (n = 32), we matched the following concepts: sense of belonging/inclusion; communication; emotional support; feeling accepted by others as a person; companionship; and practical support. We identified a new concept: support from friends/family in remaining healthy. Focus groups (n = 23) prioritized emotional support, communication, and support to remain healthy. Cognitive interviews (n = 30) found items were well-understood. The final 8-item measure performed well with patients (n = 708), with good construct validity. We used an Item Response Theory program to create a 3-item Short Form version of the measure, which captures 96% of patients indicating low social support. We developed the Multifactoral Assessment of Perceived Social Support (MAPSS) and Short Form (MAPSS-SF); brief, clinically relevant, sufficiently unidimensional measures of SS for use in HIV care.

Development and Content Validation of a Patient-Reported Sexual Risk Measure for Use in Primary Care.

BACKGROUND: Patient-provider sexual risk behavior discussions occur infrequently but may be facilitated by high-quality sexual risk screening tools. OBJECTIVE: To develop the Sexual Risk Behavior Inventory (SRBI), a brief computer-administered patient-reported measure. DESIGN: Qualitative item development/quantitative instrument validation. PARTICIPANTS: We developed SRBI items based on patient interviews (n = 128) at four geographically diverse US primary care clinics. Patients were diverse in gender identity, sex, sexual orientation, age, race/ethnicity, and HIV status. We compared sexual risk behavior identified by the SRBI and the Risk Assessment Battery (RAB) among patients (n = 422). APPROACH: We constructed an item pool based on validated measures of sexual risk, developed an in-depth interview guide based on pool content, and used interviews to elicit new sexual risk concepts. We coded concepts, matched them to item pool content, and developed new content where needed. A provider team evaluated item clinical relevance. We conducted cognitive interviews to assess item comprehensibility. We administered the SRBI and the RAB to patients. KEY RESULTS: Common, clinically relevant concepts in the SRBI included number of sex partners; partner HIV status; partner use of antiretroviral medication (ART)/pre-exposure prophylaxis (PrEP); and recent sex without barrier protection, direction of anal sex, and concern regarding HIV/STI exposure. While 90% reported inconsistent condom use on the RAB, same-day SRBI administration revealed that for over one third, all their partners were on ART/PrEP. CONCLUSION: The SRBI is a brief, skip-patterned, clinically relevant measure that ascertains sexual risk behavior across sex, sexual orientation, gender identity, partner HIV serostatus, and partner treatment status, furnishing providers with context to determine gradations of risk for HIV/STI.

Evaluation of a computer-based and counseling support intervention to improve HIV patients' viral loads.

We sought to integrate a brief computer and counseling support intervention into the routine practices of HIV clinics and evaluate effects on patients' viral loads. The project targeted HIV patients in care whose viral loads exceeded 1000 copies/ml at the time of recruitment. Three HIV clinics initiated the intervention immediately, and three other HIV clinics delayed onset for 16 months and served as concurrent controls for evaluating outcomes. The intervention components included a brief computer-based intervention (CBI) focused on antiretroviral therapy adherence; health coaching from project counselors for participants whose viral loads did not improve after doing the CBI; and behavioral screening and palm cards with empowering messages available to all patients at intervention clinics regardless of viral load level. The analytic cohort included 982 patients at intervention clinics and 946 patients at control clinics. Viral loads were assessed at 270 days before recruitment, at time of recruitment, and +270 days later. Results indicated that both the control and intervention groups had significant reductions in viral load, ending with approximately the same viral level at +270 days. There was no evidence that the CBI or the targeted health coaching was responsible for the viral reduction in the intervention group. Results may stem partially from statistical regression to the mean in both groups. Also, clinical providers at control and intervention clinics may have taken action (e.g., conversations with patients, referrals to case managers, adherence counselors, mental health, substance use specialists) to help their patients reduce their viral loads. In conclusion, neither a brief computer-based nor targeted health coaching intervention reduced patients' viral loads beyond levels achieved with standard of care services available to patients at well-resourced HIV clinics.

Reconciling the evaluation of co-morbidities among HIV care patients in two large data systems: the Medical Monitoring Project and CFAR Network of Integrated Clinical Systems.

The estimated burden of chronic disease among people living with HIV (PLWH) varies considerably by data source, due to differences in case definitions, analytic approaches, and underlying patient populations. We evaluated the burden of diabetes (DM) and chronic kidney disease (CKD) in two large data systems that are commonly queried to evaluate health issues affecting HIV care patients: the Medical Monitoring Project (MMP), a nationally representative sample, and the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS), a clinical cohort. In order to reconcile these two data sources, we addressed issues common to observational data, including selection bias, missing data, and development of case definitions. The overall adjusted estimated prevalence of DM and CKD in MMP was 12.7% and 7.6%, respectively, and the overall prevalence of DM and CKD in CNICS was 9.9% and 8.3%, respectively; prevalence estimates increased with age in both data sources. After reconciling the approach to analyzing MMP and CNICS data, sub-group specific prevalence estimates of DM and CKD was generally similar in both data sources. Both data sources suggest a considerable burden of disease among older adults in HIV care. MMP and CNICS can provide reliable data to monitor HIV co-morbidities in the US.

Content validity of Patient-Reported Outcomes Measurement Information System (PROMIS) items in the context of HIV clinical care.

PURPOSE: To assess content validity and patient and provider prioritization of Patient-Reported Outcomes Measurement Information System (PROMIS) depression, anxiety, fatigue, and alcohol use items in the context of clinical care for people living with HIV (PLWH), and to develop and assess new items as needed. METHODS: We conducted concept elicitation interviews (n = 161), item pool matching, prioritization focus groups (n = 227 participants), and cognitive interviews (n = 48) with English-speaking (~75 %) and Spanish-speaking (~25 %) PLWH from clinical sites in Seattle, San Diego, Birmingham, and Boston. For each domain we also conducted item review and prioritization with two HIV provider panels of 3-8 members each. RESULTS: Among items most highly prioritized by PLWH and providers were those that included information regarding personal impacts of the concept being assessed, in addition to severity level. Items that addressed impact were considered most actionable for clinical care. We developed additional items addressing this. For depression we developed items related to suicide and other forms of self-harm, and for all domains we developed items addressing impacts PLWH and/or providers indicated were particularly relevant to clinical care. Across the 4 domains, 16 new items were retained for further psychometric testing. CONCLUSION: PLWH and providers had priorities for what they believed providers should know to provide optimal care for PLWH. Incorporation of these priorities into clinical assessments used in clinical care of PLWH may facilitate patient-centered care.

Cumulative Incidence of Cancer Among Persons With HIV in North America: A Cohort Study.

BACKGROUND: Cancer is increasingly common among persons with HIV. OBJECTIVE: To examine calendar trends in cumulative cancer incidence and hazard rate by HIV status. DESIGN: Cohort study. SETTING: North American AIDS Cohort Collaboration on Research and Design during 1996 to 2009. PARTICIPANTS: 86 620 persons with HIV and 196 987 uninfected adults. MEASUREMENTS: Cancer type-specific cumulative incidence by age 75 years and calendar trends in cumulative incidence and hazard rates, each by HIV status. RESULTS: Cumulative incidences of cancer by age 75 years for persons with and without HIV, respectively, were as follows: Kaposi sarcoma, 4.4% and 0.01%; non-Hodgkin lymphoma, 4.5% and 0.7%; lung cancer, 3.4% and 2.8%; anal cancer, 1.5% and 0.05%; colorectal cancer, 1.0% and 1.5%; liver cancer, 1.1% and 0.4%; Hodgkin lymphoma, 0.9% and 0.09%; melanoma, 0.5% and 0.6%; and oral cavity/pharyngeal cancer, 0.8% and 0.8%. Among persons with HIV, calendar trends in cumulative incidence and hazard rate decreased for Kaposi sarcoma and non-Hodgkin lymphoma. For anal, colorectal, and liver cancer, increasing cumulative incidence, but not hazard rate trends, were due to the decreasing mortality rate trend (-9% per year), allowing greater opportunity to be diagnosed. Despite decreasing hazard rate trends for lung cancer, Hodgkin lymphoma, and melanoma, cumulative incidence trends were not seen because of the compensating effect of the declining mortality rate. LIMITATION: Secular trends in screening, smoking, and viral co-infections were not evaluated. CONCLUSION: Cumulative cancer incidence by age 75 years, approximating lifetime risk in persons with HIV, may have clinical utility in this population. The high cumulative incidences by age 75 years for Kaposi sarcoma, non-Hodgkin lymphoma, and lung cancer support early and sustained antiretroviral therapy and smoking cessation.

Age at Entry Into Care, Timing of Antiretroviral Therapy Initiation, and 10-Year Mortality Among HIV-Seropositive Adults in the United States.

BACKGROUND: The goal of targeted antiretroviral therapy initiation is to minimize disease progression among patients with human immunodeficiency virus while minimizing the therapeutic burden on these patients. We examine whether the effect of delaying therapy initiation from 500 cells/mm(3) to 350 or 200 cells/mm(3) is modified by age at entry into care. METHODS: We used the parametric g-formula to compare 10-year mortality under 3 CD4 cell count thresholds for therapy initiation among 3532 patients who entered care at 1 of 8 sites in the United States between 1998 and 2013. Results are reported separately for patients 18 to 34, 35 to 44, and 45 to 65 years of age at study entry. RESULTS: In the observed data, 10-year mortality was 13% (165 deaths). Mortality increased from 11% under therapy initiation at 500 cells/mm(3) to 12% at 350 cells/mm(3) (risk difference [RD]: 0.87; 95% confidence interval [CI]: .56, 2.17) and to 14% at 200 cells/mm(3) (RD: 2.71; 95% CI: 1.79, 5.38). The effect of delaying therapy became greater with age: RDs comparing the 350-cells/mm(3) threshold with the 500-cells/mm(3) threshold ranged from -0.03 (95% CI: -0.15, 1.76) for patients 18 to 34 years of age to 0.99 (95% CI: -.27, 1.98) for patients 35 to 44 and to 2.30 (95% CI: 1.29, 5.42) for patients 45 to 65. CONCLUSIONS: Delaying therapy increased 10-year mortality in the full cohort. Subgroup analysis highlights that patients entering care at older ages may be more vulnerable to the consequences of delayed ART initiation than younger patients.

Estimation of the standardized risk difference and ratio in a competing risks framework: application to injection drug use and progression to AIDS after initiation of antiretroviral therapy.

There are few published examples of absolute risk estimated from epidemiologic data subject to censoring and competing risks with adjustment for multiple confounders. We present an example estimating the effect of injection drug use on 6-year risk of acquired immunodeficiency syndrome (AIDS) after initiation of combination antiretroviral therapy between 1998 and 2012 in an 8-site US cohort study with death before AIDS as a competing risk. We estimate the risk standardized to the total study sample by combining inverse probability weights with the cumulative incidence function; estimates of precision are obtained by bootstrap. In 7,182 patients (83% male, 33% African American, median age of 38 years), we observed 6-year standardized AIDS risks of 16.75% among 1,143 injection drug users and 12.08% among 6,039 nonusers, yielding a standardized risk difference of 4.68 (95% confidence interval: 1.27, 8.08) and a standardized risk ratio of 1.39 (95% confidence interval: 1.12, 1.72). Results may be sensitive to the assumptions of exposure-version irrelevance, no measurement bias, and no unmeasured confounding. These limitations suggest that results be replicated with refined measurements of injection drug use. Nevertheless, estimating the standardized risk difference and ratio is straightforward, and injection drug use appears to increase the risk of AIDS.

Assessing baseline religious practices and beliefs to predict adherence to highly active antiretroviral therapy among HIV-infected persons.

The efficacy of highly active antiretroviral therapy (HAART) is dependent upon moderately high levels of adherence; however, predicting adherence before HAART initiation can be difficult. We conducted a prospective, longitudinal study among 350 HIV-infected adults attending a HIV clinic in San Diego, CA (USA) from January 2010 to December 2011 to examine both established and novel predictors of adherence, including religious practices and beliefs. Statistically significant (p < .05) variables identified in bivariate analyses were included in multivariate analyses predicting ≥90% adherence. Higher annual household income (p = .004) and religious affiliation (p = .031) were predictive of greater adherence. Participants who said their beliefs gave meaning to their lives, made them feel they had a connection with a higher being, were influential during their recovery, and helped them feel connected to humanity were more likely to be ≥90% adherent (p < .015). Conversely, participants who believed God created all things in the universe; that God will not turn his back on them; and those who regularly attended religious services, participated in religious rituals, and prayed and meditated to get in touch with God were less likely to be ≥90% adherent (p ≤ .025). Results indicate that a patient's religious beliefs and practices may predict medication adherence. Interventions should be designed to emphasize the use of positive religious coping strategies and address the adverse implications of religious fatalism.

Venous Thromboembolism Among People With HIV: Design, Implementation, and Findings of a Centralized Adjudication System in Clinical Care Sites Across the United States.

BACKGROUND: People with HIV (PWH) are at increased risk for venous thromboembolism (VTE). We conducted this study to characterize VTE including provoking factors among PWH in the current treatment era. METHODS: We included PWH with VTE between 2010 and 2020 at 6 sites in the CFAR Network of Integrated Clinical Systems cohort. We ascertained for possible VTE using diagnosis, VTE-related imaging, and VTE-related procedure codes, followed by centralized adjudication of primary data by expert physician reviewers. We evaluated sensitivity and positive predictive value of VTE ascertainment approaches. VTEs were classified by type and anatomic location. Reviewers identified provoking factors such as hospitalizations, infections, and other potential predisposing factors such as smoking. RESULTS: We identified 557 PWH with adjudicated VTE: 239 (43%) had pulmonary embolism with or without deep venous thrombosis, and 318 (57%) had deep venous thrombosis alone. Ascertainment with clinical diagnoses alone missed 6% of VTEs identified with multiple ascertainment approaches. DVTs not associated with intravenous lines were most often in the proximal lower extremities. Among PWH with VTE, common provoking factors included recent hospitalization (n = 134, 42%), infection (n = 133, 42%), and immobilization/bed rest (n = 78, 25%). Only 57 (10%) PWH had no provoking factor identified. Smoking (46%), HIV viremia (27%), and injection drug use (22%) were also common. CONCLUSIONS: We conducted a robust adjudication process that demonstrated the benefits of multiple ascertainment approaches followed by adjudication. Provoked VTEs were more common than unprovoked events. Nontraditional and modifiable potential predisposing factors such as viremia and smoking were common.